P708: CANADIAN AND RUSSIAN EXPERIENCES OF ASCIMINIB IN CHRONIC MYELOID LEUKEMIA (CML) PATIENTS WHO FAILED MULTIPLE LINES OF TYROSINE KINASE INHIBITOR (TKI) THERAPY.
Authors: F. Khadadah, A. G. Turkina, E. Lomaia, E. V. Morozova, O. A. Shukhov, A. Petrova, T. Chitanava, J. J. Vlasova, E. Kuzmina, I. Nemchenko, E. Y. Chelysheva, A. Bykova, M. Gurianova, A. Xenocostas, L. Busque, K. Jamani, S. Cerquozzi, P. Kuruvilla, R. Kaedbey, B. Leber, S. Assouline, D. D. H. Kim
Journal: HemaSphere (2022)

Background: Asciminib (ASC) is a novel, first in class 'specifically targeting the ABL myristate pocket (STAMP) inhibitor. Recent update of the ASCEMBL phase 3 data showed a superior cumulative incidence of major molecular rate (MMR) of 33.2% with ASC over bosutinib (BOS) at 18.6% by 48 weeks and higher MR4 rate (BCR-ABL1 ≤0.01%) of 14.0% with ASC over 6.6% with BOS at 48 weeks in CML patients (pts) in chronic phase (CP) who have failed at least two lines of TKI therapy. Aims: Canadian and Russian groups individually reported their real-world experiences of ASC therapy under the Managed Access Program in heavily pre-treated CML patients. Methods: Data was collected, updated and merged from 80 CML pts treated with ASC between Nov 2018 - Dec 2021 (n=57 in Russia; n=23 in Canada). Median age was 57 years (range 20-92). The median number of previous TKIs was 4 (range 2-6); Imatinib (n=74, 93%), dasatinib (n=64, 80%), nilotinib (n=58, 73%), bosutinib (n=51, 64%), ponatinib (n=35, 44%), and others (n=13, 16%). Median duration from diagnosis to ASC treatment was 92 mo (months) (range 11-310). 27 (34%) pts had a past history of clinically significant cardiovascular disease or high risk profile for cardiovascular disease. Of the 80 pts, 27 (34%) had a preexisting T315I mutation and 18 (23%) had a non-T315I mutation. Pts failed previous TKI therapy due to A)resistance or suboptimal response (n=59; 74%) and B)intolerance (n=21; 26%). BCR-ABL qPCRs were monitored at each institution. Achievement of MMR and molecular response of 4 log reduction (MR4) was assessed at 6 and 12 mo. Results: With a median of 9 mo of follow-up (range 1-38), MMR was noted in 15/68 (22%) and 14/36 pts (39%) evaluated at 6 and 12 mo, respectively. MR4 was noted in 11/68 (16%) and 9/36 pts (25%) at 6/12 mo. The cumulative incidence of MMR and MR4 was 32.6% (20.9-44.8%) and 15.9% (7.9-26.3%) at 12 mo. The probability of freedom from treatment failure (FTF) at 12 mo was 42.4% (27.6-56.4%), based on the ELN 2013 failure criteria for 2nd line therapy or beyond. In the overall population (n=80), FTF was significantly associated with reason for switch to ASC (p=0.006), and there was a trend toward association of FTF with disease phase (p=0.08) and ponatinib therapy (p=0.12), but not with ABL1 kinase domain mutation (p=0.402), additional cytogenetic abnormality (p=0.908), nor cardiovascular risk profile (p=0.345). When analysis was restricted to the patients in CML-CP (n=65), a median duration of FTF was calculated as 11.6 mo, while the 12 mo FTF rate was 46.8% (28.9-62.8%). The patients previously treated with ponatinib (n=25) showed a 27.7% (8.4-51.4%) FTF rate at 12 mo, which was lower than that in those naïve to ponatinib (n=40), 61.7% (34.9-80.2%; p=0.023). Those switched to ASC for intolerance (n=21) showed higher 12 mo FTF rate of 81.2% (41.5 -95.2%) compared to 29.4% (11.3-50.2%) in those with resistance (n=44; p=0.008). Fifteen pts discontinued ASC due to treatment failure (n=11), progression of disease to blast phase (n=3) or grade 4 thrombocytopenia (n=1). No cardiovascular event was noted. Image:Summary/Conclusion: This combined Canadian and Russian real-world experience of ASC study includes heavily pretreated CML pts including 15 pts in advanced phase. The MMR and MR4 rates were comparable in those in CP, while it was lower in non-CP pts. The 12 mo FTF rate of 42.4% was comparable to the one reported from the ASCEMBL study, 57.7%, considering that this group includes more patients who had heavily pre-treated with advanced disease. *AGT and FK contributed equally as co-first author.